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PEER-TO-PEER CLINICAL CONVERSATIONS
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EZH2 Inhibition in Prostate Cancer: MEVPRO-1 Phase III Trial Update
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Neeraj Agarwal, MD, FASCO
Zachary Klaassen is joined by Neeraj Agarwal to discuss the MEVPRO-1 study, evaluating mevrometostat, an EZH2 inhibitor, in metastatic castration-resistant prostate cancer.
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OMAHA-003 Trial Explores CYP11A1 Inhibition in Metastatic Castration-Resistant Prostate Cancer
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Evan Yu, MD
Evan Yu presents OMAHA-003, testing opevesostat, a CYP11A1 antagonist targeting one step earlier than abiraterone in steroid biosynthesis. The drug eliminates mineralocorticoids and cortisol alongside sex steroids, requiring dexamethasone and fludrocortisone replacement similar to ketoconazole.
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GUNS Trial Examines Biomarker‑Selected Neoadjuvant Approaches in High‑Risk Prostate Cancer
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Martin Gleave, CM, MD, FRCSC, FACS
Matthew Cooperberg speaks with Martin Gleave about GUNS, a neoadjuvant adaptive umbrella trial for men with high-volume, high-grade prostate cancer.
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| EZH2 Inhibition for Prostate Cancer; It’s Taken Awhile, but We Just May Be onto Something Here
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| Evan Yu, MD
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| Evan Yu reviews EZH2 as a long-sought target in prostate cancer and notes that earlier EZH2 inhibitors mostly failed to improve outcomes in mCRPC. Dr. Yu highlights encouraging data from mevrometostat plus enzalutamide, which improved radiographic progression-free survival versus enzalutamide alone and is moving into phase 3 testing.
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| Tumor Suppressor Genes in Prostate Cancer – Currently Prognostic, but Soon to Be Predictive?
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| Evan Yu, MD
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| PTEN, TP53, and RB1 are important prognostic markers in prostate cancer because they identify aggressive biology and worse outcomes, but they are not yet routine standalone treatment-selection biomarkers. The article argues they are moving toward a predictive role, especially for choosing therapies like AKT inhibitors and platinum-based chemotherapy in biomarker-enriched trials, though prospective validation is still needed.
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| Disconnect Between Evidence and Real-World Data in Metastatic Prostate Cancer
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| Christopher Sweeney, MBBS
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| Christopher Sweeney argues that there is still a major gap between trial evidence and real-world practice in metastatic hormone-sensitive prostate cancer, largely because many patients seen in clinic are older, frailer, or have comorbidities that make them ineligible for trial-style intensification. His key message is that ADT plus an ARPI should be the default backbone for most patients, with further intensification reserved for selected groups based on disease volume, fitness, access, and affordability.
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| Cabazitaxel Versus Abiraterone or Enzalutamide for Poor-prognosis Metastatic Castration-resistant Prostate Cancer after Docetaxel: A Phase 2 Trial with a Circulating Tumor DNA Analysis - Beyond the Abstract
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| Karan Parekh, Kim van der Zande, Sarah W S Ng et al.
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| In this phase 2b study of poor-prognosis mCRPC after docetaxel, cabazitaxel and ARPIs had similar 12-week clinical benefit, radiographic progression-free survival, and overall survival overall. The key nuance was that prior ARPI exposure predicted poorer outcomes with another ARPI but not with cabazitaxel, while higher ctDNA fraction and PTEN alterations were linked to worse prognosis.
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